Friday, June 24, 2016

Premature ventricular contractions: everything you wanted to know and more

A detailed review was recently
published, which should be read in the original. Below are a few key
issues covered.

Mechanisms:

Known or purported
mechanisms include automaticity, triggered activity and re-entry.
Automaticity causes ventricular ectopy (VE) by premature
depolarization of pacemaker cells. This results from a shortening of
the time it takes for phase 4 diastolic depolarization to reach
threshold, due to an increased slope of diastolic depolarization or
other mechanisms.

So called
triggered activity is the result of afterdepolarizations, which could
take the form of delayed (DAD) or early afterdepolarizations (EAD).
DAD occur in phase 4 and are believed to be related to increased
intracellular calcium concentrations due to a variety of mechanisms
(eg catecholamine effects) with increased cAMP levels as a final
common pathway. This in turn leads to a transient inward
depolarizing sodium current generated by the Na/Ca exchanger. DAD is
believed to be the mechanism of adenosine sensitive RVOT ectopy.

The mechanisms of
EAD are less clear. Because EAD occur in phase 3 they increase
repolarization time and appear to be instrumental in causing
arrhythmias in the setting of a long QT interval.

Re-entry, once
thought to be the primary mechanism of VE, is now in doubt as an
important cause of PVCs.

The PVC coupling
interval may provide a clue as to the mechanism but this is not
entirely clear. A fixed coupling interval implies re-entry (if such
exists in man) or triggered activity. Variable coupling intervals
imply automaticity. Variable coupling intervals with equal or
mathematically related inter-ectopic intervals are designated as
parasystole which is usually associated with structural heart
disease.

Are PVCs associated with harm?

It is useful to
approach this question with respect to the presence or absence of
structural heart disease. In both acute ischemia and chronic
structural heart disease we know that they are associated with
negative outcomes though it is less clear whether as a marker or a
cause.

What about
patients with no structural heart disease? In such patients VE was
traditionally thought to be almost universally benign, based
primarily on this paper from 1985 by Harold Kennedy and
others. Drawing from a larger database that has accumulated since
that time, this notion has been challenged, and there may be risk in
some patients. This risk is poorly characterized with the exception
of two categories: certain purely electrical heart diseases
(channelopathies) and the potential for chronic frequent PVCs to
cause a dilated cardiomyopathy (DCM). In purely electrical diseases
a single PVC may trigger a life threatening event. From the article:

PVCs can trigger
VF or polymorphic VT in patients with or without structural heart
disease. 6 30 Some features of PVCs can help to identify “malignant
PVCs” that have the potential of triggering VF in some patients.
Most often PVCs are not tightly coupled to prior sinus beats;
however, in certain conditions, tightly coupled PVCs have been
described to trigger VF. This has been described for patients with
Brugada syndrome, 31 early repolarization syndromes, 32 idiopathic
VF, 33 or in the setting of acute myocardial infarction. 7 In the
absence of these conditions, malignant ventricular arrhythmias are
rare but have been reported and often have been triggered by tightly
coupled PVCs. 6 34 No absolute cutoff value for a tight coupling
interval has been defined, although most often the PVC coupling
interval was less than 400 ms in these circumstances. 6 Other
parameters that need to be assessed include the QT interval and the
presence of nonsustained VT, including rate and morphology. More
malignant arrhythmias have shorter cycle lengths, 35 and in 1 report,
the coupling interval of the second beat of the nonsustained VT was
found to be shorter in patients with VF compared with patients
without VF. 36

It must be kept in
mind that in some conditions (eg LQTS, hereditary and acquired) not
all triggering PVCs are short coupled.

Concerning PVC
induced DCM recent findings challenge the notion that this is caused
chiefly by RVOT ectopy. Though RVOT ectopy is a known cause, DCM can
result from VE originating from other foci. Also recently challenged
is the idea that 15% of heartbeats is necessarily the ectopic
frequency threshold for the development of DCM. The critical
frequency is actually quite variable and is likely influenced by
other risk factors, one of which is PVC QRS width, which is roughly
directly proportional to the risk of DCM. A cutoff of 150 ms has
been suggested. Epicardial origin of PVCs is associated with a wider
QRS and greater DCM risk. Finally, interpolation of PVCs is also
associated with a greater DCM risk. PVC induced DCM was once thought
to be a variant of tachycardia mediated DCM but is now believed due
to different mechanisms. It should be noted that in patients who
already have structural disease for other reasons, frequent PVCs can
lead to further deterioration of ventricular function.

Treatment:

Beta blockers are
first line despite low efficacy due to their favorable safety
profile. I-C antiarrhythmic drugs have stronger efficacy and are
considered the next line of treatment provided the patient has no
structural heart disease. The concern that these drugs increase the
risk of SCD when used to treat PVCs is restricted to patients with
structural heart disease. Careful assessment and appropriate
expertise are required. Amiodarone is an option for patients who do
have structural heart disease. Once DCM ensues due to frequent PVCs
therapeutic options become limited for the above stated reasons.
Suppression of VE with amiodarone has been reported to reverse DCM in
that situation.

Catheter ablation
is a preferred option in selected patients and is discussed in detail
in the article.